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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 1088-1096. doi: 10.19723/j.issn.1671-167X.2023.06.021

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Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody

Yan-hong MENG1,Yi-fan CHEN2,Pei-ru ZHOU3,*()   

  1. 1. Department of Clinical Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
    2. Department of Information Center, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
    3. Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
  • Received:2022-10-09 Online:2023-12-18 Published:2023-12-11
  • Contact: Pei-ru ZHOU E-mail:zhoupeiru1989@163.com
  • Supported by:
    the Program for New Clinical Techniques and Therapies of Peking University School and Hospital of Stomatology(PKUSSNCT-21B13)

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Abstract:

Objective: To investigate the clinical and immunological features of primary Sjögren's syndrome (pSS) patients with positive anti-centromere protein B (CENP-B) antibody. Methods: In this cross-sectional study, the general clinical data, radiographic examination and labial salivary gland biopsy data, and serum immunological and biochemical data of patients diagnosed with pSS from January 2016 to August 2022 were evaluated. The included patients were divided into the anti-CENP-B antibody positive and negative groups. Intergroup differences were analyzed with SPSS 23.0 software. Subgroup analysis was further performed by dividing the anti-CENP-B antibody positive group into the single anti-CENP-B antibody positive and with other auto-antibodies positive groups to determine the characters related to anti-CENP-B antibody. Results: In this study, 288 patients with pSS were evaluated, including 75 patients with anti-CENP-B antibody positive and 213 with anti-CENP-B antibody negative. Univariate analysis showed that compared with the anti-CENP-B antibody negative group, the patients of the anti-CENP-B antibody positive group were older, had lower proportion of the patients with salivary gland enlargement and higher proportion of autoimmune liver disease. As for immunological indicators, the positive proportions of anti-SSA/Ro60, anti-Ro52, and anti-SSB antibodies were significantly lower. Moreover, the immunoglobulin (Ig) G and rheumatoid factor levels were significantly lower, while the IgM level was significantly higher in the patients of the anti-CENP-B antibody positive group. As for serum biochemical indicators, for the patients of the anti-CENP-B antibody positive group, the level of total protein (TP) was lower, the albumin/globulin ratio was higher, and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) were higher. Subgroup analysis showed that the levels of TP and IgA in the patients of the single anti-CENP-B antibody positive group were significantly lower than those of the patients with other autoantibodies positive group. Conclusion: The pSS patients with anti-CENP-B antibody positive have unique clinical and immunological features of lower disease activity, less likely to involve salivary gland, higher risk for autoimmune liver disease, and higher levels of liver function indicators. Anti-CENP-B antibody may be a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome.

Key words: Centromere protein B antibody, Primary Sjögren's syndrome, Autoantibodies, Immuno-logical features

CLC Number: 

  • R593.2

Figure 1

The flow diagram of screening and grouping of pSS patients pSS, primary Sjögren's syndrome; SGE, salivary gland enlargement; ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; CENP-B, centromere protein B."

Table 1

Comparison of the clinical features of the anti-CENP-B antibody positive and negative pSS patients"

Characteristics Anti-CENP-B antibody (-)(n=213) Anti-CENP-B antibody (+)(n=75) P
Gender, n (%) 0.927
  Male 11 (5.2) 3 (4.0)
  Female 202 (94.8) 72 (96.0)
Age at diagnosis/years, M (P25, P75) 53.0 (38.5, 62.0) 63.0 (54.0, 71.0) < 0.001
Dry mouth symptom duration/months, M (P25, P75) 24 (6, 72) 36 (12, 60) 0.335
UWS ≤0.1 mL/min*, n/total (%) 112/116 (96.6) 42/44 (95.5)
Salivary glands enlargement, n (%) 98 (46.0) 22 (29.3) 0.012
Abnormal conventional X-ray sialography*, n/total (%) 138/151 (91.4) 37/43 (86.0)
LSG biopsy*, n/total (%)
  FLS and FS = 1 foci/4 mm2 10/39 (25.6) 8/33 (24.2)
  FLS and FS = 2 foci/4 mm2 8/39 (20.5) 5/33 (15.2)
  FLS and FS = 3 foci/4 mm2 3/39 (7.7) 4/33 (12.1)
  FLS and FS ≥ 4 foci/4 mm2 18/39 (46.2) 16/33 (48.5)
Dry eyes symptom, n (%) 127 (59.6) 52 (69.3) 0.136
Abnormal Schirmer’s test* or OSS*, n (%) 69 (32.4) 26 (34.7)
Joint involvement, n (%) 41 (19.2) 21 (28.0) 0.113
Hypertension, n (%) 39 (18.3) 15 (20.0) 0.747
Autoimmune liver disease, n (%) 1 (0.5) 4 (5.3) 0.024

Table 2

Comparison of autoantibodies and other immune indicators between groups"

Characteristics Anti-CENP-B antibody (-)(n=213) Anti-CENP-B antibody (+)(n=75) P
Anti-mitochondrial antibody M2, n (%) 12 (5.6) 7 (9.3) 0.401
Anti-ribosomal P-proteins antibody, n (%) 9 (4.2) 3 (4.0) > 0.999
Anti-histones antibody, n (%) 6 (2.8) 1 (1.3) 0.778
Anti-nucleosome antibody, n (%) 3 (1.4) 6 (8.0) 0.015
Anti-dsDNA antibody, n (%) 9 (4.2) 3 (4.0) > 0.999
Anti-PCNA antibody, n (%) 1 (0.5) 0 (0) > 0.999
Anti-Jo-1 antibody, n (%) 5 (2.3) 1 (1.3) 0.953
Anti-PM-Scl antibody, n (%) 5 (2.3) 1 (1.3) 0.953
Anti-Scl-70 antibody, n (%) 3 (1.4) 2 (2.7) 0.839
Anti-SSB antibody, n (%) 108 (50.7) 10 (13.3) < 0.001
Anti-Ro52 antibody, n (%) 178 (83.6) 39 (52.0) < 0.001
Anti-SSA/Ro60 antibody, n (%) 190 (89.2) 36 (48.0) < 0.001
Anti-Sm antibody, n (%) 4 (1.9) 4 (5.3) 0.247
Anti-nRNP/Sm antibody, n (%) 17 (8.0) 3 (4.0) 0.243
IgG/(g/L), M (P25, P75) 19.55 (16.24, 24.73) 17.90 (13.51, 19.12) < 0.001
IgA/(g/L), M (P25, P75) 2.91 (2.33, 3.65) 2.91 (2.03, 3.50) 0.154
IgM/(g/L), M (P25, P75) 1.34 (0.92, 1.65) 1.34 (1.07, 2.42) 0.017
C3/(g/L), ${\bar x}$±s 1.313±0.238 1.310±0.227 0.074
RF/(g/L), M (P25, P75) 30.47 (19.30, 105.89) 18.20 (5.55, 30.42) < 0.001

Table 3

Multivariate analysis of anti-CENP-B antibody and immunoglobulins by binary Logistic regression"

Items P value OR (95% CI)
IgG* < 0.001 0.897 (0.850-0.947)
IgM* 0.007 1.321 (1.079-1.618)

Table 4

Comparison of serum biochemical indexes between groups"

Characteristics Anti-CENP-B antibody (-) (n=213) Anti-CENP-B antibody (+) (n=75) P
TP/(g/L), M (P25, P75) 80.0 (75.7, 84.0) 75.0 (72.0, 81.0) < 0.001
Alb/(g/L), M (P25, P75) 43.7 (41.7, 46.0) 44.0 (42.3, 46.0) 0.372
A/G, ${\bar x}$±s 1.240±0.270 1.410±0.266 < 0.001
ALT/(U/L), M (P25, P75) 16.0 (12.0, 21.8) 19.5 (14.0, 28.0) 0.014
AST/(U/L), M (P25, P75) 20.0 (17.0, 26.0) 24.0 (19.0, 31.0) 0.001
AST/ALT, M (P25, P75) 1.29 (1.00, 1.61) 1.31 (1.09, 1.45) 0.089
TBIL/(μmol/L), M (P25, P75) 12.08 (9.80, 15.87) 12.54 (10.10, 15.01) 0.777
DBIL/(μmol/L) M (P25, P75) 2.91 (2.26, 3.80) 3.20 (2.47, 4.05) 0.188
ALP/(U/L), M (P25, P75) 73.0 (67.0, 80.0) 73.0 (70.0, 99.0) 0.034
GGT/(U/L), M (P25, P75) 18.0 (14.9, 20.0) 18.0 (14.0, 35.0) 0.046
CK/(U/L), M (P25, P75) 64.0 (55.0, 73.5) 64.0 (52.0, 81.0) 0.652
LDH/(U/L), M (P25, P75) 171.0 (152.5, 175.0) 171.0 (171.0, 194.0) < 0.001

Table 5

Subgroup analysis according to the positive status of anti-CENP-B antibody and other autoantibodies"

Characteristics Anti-CENP-B antibody (+) alone(n=24) Anti-CENP-B and other autoantibodies (+)(n=51) P
IgA/(g/L), M (P25, P75) 2.11 (1.78, 2.91) 2.91 (2.24, 3.74) 0.027
TP/(g/L), M (P25, P75) 72.6 (69.2, 76.5) 76.6 (73.0, 82.0) 0.032
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